Regiodivergent Reaction

An yttrium salen catalyst prompts trimethylsilylazide to open a racemic mix of aziridines in a regiodivergent manner.

An yttrium salen catalyst prompts trimethylsilylazide to open a racemic mix of aziridines in a regiodivergent manner.

A single catalyst that transforms a racemic mixture of aziridines into a pair of regioisomeric products has been developed by chemists at Ohio State Universtity. The reaction converts all the starting material in good yield and with exceptionally high enantioselectivity (Science2009,326, 1662).

A meager 50% yield is usually the best a chemist can hope for when using a ring-opening reaction to sort the enantiomers in a racemic mix of strained, three-membered-ring heterocycles, such as aziridines or epoxides. That’s because most catalysts resolve the mixture by opening one enantiomer, leaving the other untouched.

In the new reaction, “each enantiomer reacts with the catalyst to give a different product,” explains Jon R. Parquette, who discovered the regiodivergent transformation along with colleagues T. V. RajanBabu and Bin Wu. In the presence of an yttrium salen catalyst, trimethylsilylazide attacks aziridines with R stereochemistry at one carbon and aziridines with S stereochemistry at the other. Enantiomeric excess of the resulting ring-opened products is 90 to 99%, depending on the substituents.

Although conceptually similar reactions have been reported previously, “this level of selectivity has never been seen before,” notes RajanBabu. The catalyst induces regiodivergent products even when the aziridines differ only by the placement of a methyl group. The researchers suspect the selectivity arises from the nature of the dimeric catalyst’s cavity and are currently working to elucidate the mechanism and improve the reaction’s efficiency.

“This is a nice illustration of parallel kinetic resolution with its most noteworthy feature being the ability to convert simple starting materials into valuable small-molecule building blocks,” comments Mark Lautens, a chemistry professor at the University of Toronto.

“The kinetic resolution of a racemic compound through regiochemically divergent pathways illustrates an interesting strategy for the synthesis of enantiomerically pure compounds,” says Geoffrey W. Coates of Cornell University. “The field of synthesis will greatly benefit if this strategy can be rationally applied for other kinetic resolutions.”